title: Increased risk of high-grade hemorrhage in cancer patients treated with gemcitabine: a meta-analysis of 20 randomized controlled trials.
abstract: OBJECTIVE
  Gemcitabine, a third-generation anticancer agent, has been shown to be active in several solid tumors. High-grade hemorrhage (grade ≥ 3) has been reported with this drug, although the overall risk remains unclear. We conducted a meta-analysis of randomized controlled trials evaluating the incidence and risk of high-grade hemorrhage associated with gemcitabine.
  
  
  METHODS
  Pubmed was searched for articles published from January 1, 1990 to December 31, 2012. Eligible studies included prospective randomized controlled phase II and III trials evaluating gemcitabine-based vs non-gemcitabine-based therapy in patients with solid tumors. Data on high-grade hemorrhage were extracted. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of included trials.
  
  
  RESULTS
  A total of 6433 patients from 20 trials were included. Among patients treated with gemcitabine-based chemotherapy, the overall incidence of high-grade hemorrhage was 1.7% (95%CI: 0.9-3.1%), and the RR of high-grade hemorrhage was 2.727 (95%CI: 1.581-4.702, p<0.001). Exploratory subgroup analysis revealed the highest RR of hemorrhage in non-small-cell lung cancer (NSCLC) patients (RR: 3.234; 95%CI, 1.678-6.233; p<0.001), phase II trials (RR 7.053, 95%CI: 1.591-31.27; p = 0.01), trials reported during 2006-2012 (RR: 3.750; 95%CI: 1.735-8.108, p<0.001) and gemcitabine used as single agent (RR 7.48; 95%CI: 0.78-71.92, p = 0.081).
  
  
  CONCLUSIONS
  Gemcitabine is associated with a significant increase risk of high-grade hemorrhage in patients with solid tumors when compared with non-gemcitabine-based therapy.
authors.affiliation: Department of Oncology, Chinese PLA General Hospital, BeiJing City, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Jingliang
authors.initials: J
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Tao
authors.forename: Baishou
authors.initials: B
authors.lastname: Wu
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Yao
authors.initials: Y
authors.lastname: Cheng
authors.forename: Weiwei
authors.initials: W
authors.lastname: Dong
authors.forename: Ruixin
authors.initials: R
authors.lastname: Li
mesh_terms: D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D009369:Neoplasms / Q000188:drug therapy*; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine